The principal objective of the proposed project is to identify whether changes in the intracellular concentration of cyclic 3'5' nucleotides are associated with alterations in the function of alveolar macrophages (i.e., rabbit lung lavage cells). The activation of alveolar macrophages will be examined in vitro by measuring changes in MIF activity, glucose oxidation through the hexose monophosphate shunt, and lysosomal enzyme content. The latter three parameters of alveolar macrophage activation will be performed under conditions that will allow intracellular levels of cyclic AMP and cyclic GMP to be measured at the same time. Consequently, these experiments will provide a more accurate assessment of the temporal association between any changes in cell function and cyclic nucleotide levels. Some experiments will involve the direct antigen activation of alveolar macrophages from immunized rabbits. Other in vitro studies will use the indirect activation of alveolar macrophages by lymphokine containing supernatants. Attempts will also be made to assess the in vivo $ time course of such changes if in vitro changes are noted. Alveolar macrophages from normal and immunized rabbits will be compared in terms of their release of certain lysosomal enzymes (i.e., Beta-glucuronidase) in the presence of phagocytizable particles such as polystyrene latex beads. The ability of drugs or hormones to alter these alveolar macrophage functions and cyclic nucleotide levels will also be assessed.